Qing Li1, Wei Peng1, Jiao Wu1, Xianfei Wang2, Yixing Ren3, Huan Li1, Yan Peng1, Xiaowei Tang1, Xiangsheng Fu4. 1. Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Sichuan, China. 2. Department of Gastroenterology, The Second Affiliated Hospital of North Sichuan Medical College, Sichuan, China. 3. Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Sichuan, China. 4. Department of Gastroenterology, The Affiliated Hospital of North Sichuan Medical College, Sichuan, China.
Abstract
Objectives: The interaction between the quorum sensing (QS) molecules of gut microbiota and the immunity of colorectal cancer (CRC) has not been investigated before. Methods: We measured the concentration of autoinducer-2 (AI-2) in samples of stool, colorectal tissue, saliva and serum of CRC patients, and compared this to AI-2 levels in colorectal adenoma (AD) and normal colon mucosa (NC). To explore the activated signaling pathways involved, we utilized AI-2 extracted from Fusobacterium nucleatum to stimulate macrophages and validated these in vitro findings in human CRC tissues. Results: The AI-2 concentration in both colorectal tissue and stool of CRC patients was significantly higher when compared to that in AD and NC (all P values < .01). The AI-2 concentration along with the progression of CRC in both tissues and stools was significantly increased (P= .045，P= .0003, respectively). After AI-2 stimulation, TNFSF9 was the most significantly increased protein in macrophage cells (P < .01). TNFSF9 expression was significantly higher in CRC tissues when compared to NCs (P< .0001), which was mainly derived from macrophages in the tumor microenvironment. Moreover, AI-2 level was positively associated with CD3 + T cell numbers (P= .0462), and negatively associated with CD4/CD8 ratio (P= .0113) within CRC tissues. Conclusions: We demonstrated for the first time that AI-2 may serve as a novel marker for screening CRC in the clinic. AI-2 was associated with tumor immunity in CRCs through tumor-associated macrophages and CD4/CD8 ratio in a TNFSF9-dependent manner.
Objectives: The interaction between the quorum sensing (QS) molecules of gut microbiota and the immunity of colorectal cancer (CRC) has not been investigated before. Methods: We measured the concentration of autoinducer-2 (AI-2) in samples of stool, colorectal tissue, saliva and serum of CRCpatients, and compared this to AI-2 levels in colorectal adenoma (AD) and normal colon mucosa (NC). To explore the activated signaling pathways involved, we utilized AI-2 extracted from Fusobacterium nucleatum to stimulate macrophages and validated these in vitro findings in humanCRC tissues. Results: The AI-2 concentration in both colorectal tissue and stool of CRCpatients was significantly higher when compared to that in AD and NC (all P values < .01). The AI-2 concentration along with the progression of CRC in both tissues and stools was significantly increased (P= .045，P= .0003, respectively). After AI-2 stimulation, TNFSF9 was the most significantly increased protein in macrophage cells (P < .01). TNFSF9 expression was significantly higher in CRC tissues when compared to NCs (P< .0001), which was mainly derived from macrophages in the tumor microenvironment. Moreover, AI-2 level was positively associated with CD3 + T cell numbers (P= .0462), and negatively associated with CD4/CD8 ratio (P= .0113) within CRC tissues. Conclusions: We demonstrated for the first time that AI-2 may serve as a novel marker for screening CRC in the clinic. AI-2 was associated with tumor immunity in CRCs through tumor-associated macrophages and CD4/CD8 ratio in a TNFSF9-dependent manner.
Authors: Franck Pagès; Bernhard Mlecnik; Florence Marliot; Gabriela Bindea; Fang-Shu Ou; Carlo Bifulco; Alessandro Lugli; Inti Zlobec; Tilman T Rau; Martin D Berger; Iris D Nagtegaal; Elisa Vink-Börger; Arndt Hartmann; Carol Geppert; Julie Kolwelter; Susanne Merkel; Robert Grützmann; Marc Van den Eynde; Anne Jouret-Mourin; Alex Kartheuser; Daniel Léonard; Christophe Remue; Julia Y Wang; Prashant Bavi; Michael H A Roehrl; Pamela S Ohashi; Linh T Nguyen; SeongJun Han; Heather L MacGregor; Sara Hafezi-Bakhtiari; Bradly G Wouters; Giuseppe V Masucci; Emilia K Andersson; Eva Zavadova; Michal Vocka; Jan Spacek; Lubos Petruzelka; Bohuslav Konopasek; Pavel Dundr; Helena Skalova; Kristyna Nemejcova; Gerardo Botti; Fabiana Tatangelo; Paolo Delrio; Gennaro Ciliberto; Michele Maio; Luigi Laghi; Fabio Grizzi; Tessa Fredriksen; Bénédicte Buttard; Mihaela Angelova; Angela Vasaturo; Pauline Maby; Sarah E Church; Helen K Angell; Lucie Lafontaine; Daniela Bruni; Carine El Sissy; Nacilla Haicheur; Amos Kirilovsky; Anne Berger; Christine Lagorce; Jeffrey P Meyers; Christopher Paustian; Zipei Feng; Carmen Ballesteros-Merino; Jeroen Dijkstra; Carlijn van de Water; Shannon van Lent-van Vliet; Nikki Knijn; Ana-Maria Mușină; Dragos-Viorel Scripcariu; Boryana Popivanova; Mingli Xu; Tomonobu Fujita; Shoichi Hazama; Nobuaki Suzuki; Hiroaki Nagano; Kiyotaka Okuno; Toshihiko Torigoe; Noriyuki Sato; Tomohisa Furuhata; Ichiro Takemasa; Kyogo Itoh; Prabhu S Patel; Hemangini H Vora; Birva Shah; Jayendrakumar B Patel; Kruti N Rajvik; Shashank J Pandya; Shilin N Shukla; Yili Wang; Guanjun Zhang; Yutaka Kawakami; Francesco M Marincola; Paolo A Ascierto; Daniel J Sargent; Bernard A Fox; Jérôme Galon Journal: Lancet Date: 2018-05-10 Impact factor: 79.321
Authors: Mark E Dudley; John R Wunderlich; Paul F Robbins; James C Yang; Patrick Hwu; Douglas J Schwartzentruber; Suzanne L Topalian; Richard Sherry; Nicholas P Restifo; Amy M Hubicki; Michael R Robinson; Mark Raffeld; Paul Duray; Claudia A Seipp; Linda Rogers-Freezer; Kathleen E Morton; Sharon A Mavroukakis; Donald E White; Steven A Rosenberg Journal: Science Date: 2002-09-19 Impact factor: 47.728